The objectives of the proposed research are to investigate synapses and simple neuronal pathways using the techniques of electron microscopy. An ongoing program of comparative ultrastructural studies on neurons and synapses in simple nervous systems will be continued using standard transmission electron microscopy (TEM). This is expected to provide a morphological basis for postulating a logical hypothesis of origin and evolution of the nervous system. Isolated neurons of Hydra will be studied by scanning electron microscopy (SEM) to determine neuronal shapes and if possible the external sites of synaptic contacts. An attempt will be made to reconstruct the entire nervous system of a simple metazoan, Hydra littoralis, by high-voltage electron microscopy (HVEM) of serial thick sections. The nerve cell processes will be traced and aligned by computer and the profiles displayed in three dimensions using a computer reconstruction method. It is expected that the relatively new approach of HVEM for biological work combined with computer methods for three dimensional reconstruction of neuronal organization will provide a new way of answering questions about synapses and neuronal pathways. Such techniques may then be applied to the more complex study of the CNS in normal and diseased states as well as the pathways of innervation and nerve-muscle relationships in such diseases as muscular dystrophy and myasthenia gravis.